Osteoclasts are large multinuclear cells which function to erode bone matrix. They are related to macrophage and other cells that develop from monocyte cells. Like macrophage, osteoclasts are derived from haematopoietic progenitor cells.
Bone matrix erosion is a normal process which occurs in coordination with bone matrix formation, a process in which osteoblasts are involved. Essentially, osteoclasts erode bone matrix and tunnel into bone while osteoblasts follow, line the walls of the tunnel and form new bone matrix. Typically, in a normal adult, about 5-10% of bone is replaced by these processes annually.
Bone diseases such as osteoporosis and Paget's disease are characterized by a loss of bone. Similarly, metastatic bone disease, rheumatoid arthritis and peridontal bone disease are also characterized by bone loss. In many cases, bone loss leads to fractures in patients. In addition to the pain and suffering, patients become physically impaired which often leads to complications having negative consequences on patient health and quality of life. Moreover, the economic costs attributable to these diseases are tremendous.
Receptors and ligands of the Tumor Necrosis Factor family have recently been shown to play an essential part in the differentiation and activity of osteoclasts. On the one hand, Tumor Necrosis Factor-α (TNF-α) is known to promote osteoclastogenesis. On the other hand, a TNF-like molecule present on and/or secreted by osteoclasts and stromal cells, referred to interchangeably in the field and herein as Receptor activator of NF-κB ligand, (RANKL), Osteoclast differentiation factor (ODF), Osteoprotegerin ligand (OPGL), and TNF-related activation-induced cytokine (TRANCE), interacts with a TNF-receptor-like molecule, referred to in the field and herein as Receptor activator of NF-κB ligand, (RANK), which present in the membranes of osteoclast precursors and mature osteoclasts to regulate osteoclastogenesis and the resorbing activity of mature osteoclasts. The utilization of TNF-α antagonists, such as a monoclonal antibodies, for therapeutic purposes, has proven difficult, however, because of immunity to the large molecule, and limited entry into some specialized compartments of the body. Suda, et al. 1999 Endocrine Reviews 20(3):345-357, which is incorporated herein by reference, describes osteoclast differentiation and function. Filvaroff, E and R. Derynck 1998 Curr. Biol. 8:R679-R682, which is incorporated herein by reference, refer to bone remodeling and a signaling system for osteoclast regulation.
There is a need for methods of regulating osteoclastogenesis and the resorbing activity of mature osteoclasts. There is a need for methods of preventing bone loss and treating bone diseases.